The objective of this proposal is to determine the role of prostaglandins and cyclic nucleotides in immunological and inflammatory reactions and investigate means whereby these compounds might modulate inflammation and tissue injury. The response (prostaglandin and cyclic nucleotide production, enzyme release) of synovial cells in tissue culture to challenge by immune complexes and soluble and particulate antigens will be studied. Biochemical responses will be correlated with synovial cell ultrastructure. Lymphocytes from patients with multiple sclerosis (MS) adhere in significantly greater numbers to measles virus infected human epithelial (HEp-2) cells than lymphocytes from healthy controls. Increased adherence appears to be due in part to a prostaglandin sensitive event. We will study the mechanisms responsible (prostaglandin cyclic nucleotide relationships) for increased lymphocyte adherence in MS. Prostaglandin E1 (PGE1) treatment of NZB/W mice prevents nephritis and increases survival of these animal models of human systemic lupus erythematosus. We will study the effect of PGE1 on immune responses in NZB/W mice, and the effect on lymphocte function in normal volunteers.